Conversion of succinyl-CoA

Figure 16-2. The citric acid cycle the major catabolic pathway for acetyl-CoA in aerobic organisms. Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, is taken into the cycle, together with HjO, and oxidized to CO2 with the release of reducing equivalents (2H). Subsequent oxidation of 2H in the respiratory chain leads to coupled phosphorylation of ADP to ATP. For one turn of the cycle, 11 are generated via oxidative phosphorylation and one arises at substrate level from the conversion of succinyl-CoA to succinate.

Conversion of Succinyl-CoA to Succinate Succinyl-CoA, like acetyl-CoA, has a thioester bond with a strongly negative standard free energy of hydrolysis (AG ° = -36 kJ/mol). In the next step of the citric acid cycle, energy released in the breakage of this bond is used to drive the synthesis of a phosphoanhydride bond in either GTP or ATP, with a net AG ° of only -2.9 kJ/mol. Succinate is formed in the process ... 

Although the citric acid cycle directly generates only one ATP per turn (in the conversion of succinyl-CoA to succinate), the four oxidation steps in the cycle provide a large flow of electrons into the respiratory chain via NADH and FADH2 and thus lead to formation of a large number of ATP molecules during oxidative phosphorylation. 

Succinate Thiokinase Couples the Conversion of Succinyl-CoA to Succinate with the Synthesis of GTP... 

Conversion of succinyl CoA to succinate [catalyzed by succinyl CoA synthetase the reaction requires inorganic phosphate and GDP (or ADP)]. 

Each of the three NADH molecules produced per turn of the cycle yields 3 ATPs and the single FADH2 yields 2 ATPs by oxidative phosphorylation (although some measurements indicate that the quantities are 2.5 and 1.5 respectively - see p. 355). One GTP (or ATP) is synthesized directly during the conversion of succinyl CoA to succinate. Thus the oxidation of a single molecule of glucose via the citric acid cycle produces 12 ATP molecules. 

Problem 29.10 Write a mechanism for the conversion of succinyl CoA to succinate in step 5 of the citric acid cycle. 

The activation occurs at the expense of conversion of succinyl-CoA to succinate in the TCA cycle and formation of GTP (Chapter 13). Acetoacetyl-CoA is cleaved to two molecules of acetyl-CoA by acetyl-CoA acetyItransferase, the same enzyme involved in the synthesis of acetoacetyl-CoA (Figure 18-9). Acetyl-CoA is oxidized in the TCA cycle. Thus, formation of ketone bodies in the liver and their oxidation in extrahepatic tissues are dictated by the ratio [substrates]/[products]. 

The conversion of succinyl-CoA to succinate yields the only high-energy phosphate bond to be formed directly in the course of the cycle, lliis reaction is an example of a sutetrate level phosphorylation (page 228). 

Succinyl CoA-ADP phosphorylase —conversion of succinyl CoA to succinate with concomitant esterification of inorganic phosphate. 

Both phosphate ions and one of the adenine nucleotides must be added to freshly prepared mitochondrial suspensions (in sucrose or dilute KCl) for citric-acid cycle oxidations to proceed at maximal velocity. The conversion of succinyl CoA to succinate is one of several processes which depend upon both inorganic phosphate (Pi) and ADP. The formal equation for this conversion is as follows ... 

Whiteley (396-398) prepared cell-free extracts of Micrococcus lactilyticus which were very active in catalyzing the decarboxylation of succinate at a pH optimum of 5.2, and with a partial requirement for Mg++ and possibly diphosphothiamine. Treatment of the extracts with anion-exchange resins makes the reaction dependent on the addition of both ATP and CoA. Under these conditions they can also be shown to convert succinate to succinyl-CoA. These extracts catalyze the evolution of CO from succinyl-CoA in the absence of added cofactors. Some evidence was obtained for the production of succinate from propionate and CO in the presence of ATP and CoA. Since decarboxylation of relatively large amounts of succinate occurs with catal rtic amounts of ATP and CoA, Whiteley postulated a conversion of succinyl-CoA to CO and propionyl-CoA followed by transfer of CoA from propionyl-CoA to succinate (Scheme 3). The transfer of CoA would be catalyzed by an enzyme analogous to Stadtman s CoA transphorase (325), which is present in the bacterial extracts. 

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